Durvalumab With Stereotactic Body Radiation Therapy (SBRT) vs Placebo With SBRT in Early Stage Unresected Non-small Cell Lung Cancer (NSCLC) Patients/ Osimertinib Following SBRT in Patients With Early Stage Unresected NSCLC Harboring an EGFR Mutation
PACIFIC-4
A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab With Stereotactic Body Radiation Therapy (SBRT) for the Treatment of Patients With Unresected Stage I/II, Lymph-node Negative Non-small Cell Lung Cancer (PACIFIC-4/RTOG-3515) Osimertinib Following SBRT, a Single Arm Cohort for Patients With Unresected Stage I/II, Lymph Node Negative NSCLC Harboring a Sensitizing EGFR Mutation
2 other identifiers
interventional
724
20 countries
209
Brief Summary
This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus placebo with SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC. An additional cohort will assess Osimertinib following SBRT in patients with early stage unresected T1 to T3N0M0 NSCLC harbouring an EGFR mutation.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2019
Longer than P75 for phase_3
209 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 25, 2019
CompletedFirst Posted
Study publicly available on registry
February 6, 2019
CompletedStudy Start
First participant enrolled
March 6, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 31, 2028
April 23, 2026
April 1, 2026
9.7 years
January 25, 2019
April 22, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1 in subpopulation of patients with Stage I/II NSCLC
Main Cohort
from randomization up to 6 years
4-year Progression-Free Survival (4y-PFS) by ICR according to RECIST 1.1 criteria
Osimertinib Cohort
from treatment start up to 5 years
Secondary Outcomes (19)
Progression-Free Survival (PFS) assessed by BICR per RECIST 1.1 in all randomised patients with Stage I/II NSCLC
from randomization up to 6 years
Overall Survival (OS)
from randomization up to 7 years
Concentration of durvalumab in serum such as peak concentration and trough
12 weeks after last dose
Detection of ADA neutralising antibodies titers
up to 6 months after last dose
Health-related quality of life in patients treated with durvalumab with SoC SBRT compared to placebo with SoC SBRT using the EORTC QLQ-C30
from randomization up to 7 years
- +14 more secondary outcomes
Other Outcomes (2)
Lung cancer mortality
from treatment start up to 5 years
Lung Cancer Mortality
from randomization Up to 5 years
Study Arms (3)
SoC SBRT + Durvalumab Therapy (Main Cohort)
EXPERIMENTALSBRT Durvalumab (PD-L1 monoclonal antibody) 1500 mg every 4 weeks \[q4w\] intravenously \[iv\] for up to 26 cycles or until progression or other discontinuation criteria are met.
SoC SBRT + Placebo Therapy (Main Cohort)
PLACEBO COMPARATORSBRT Placebo (matching placebo for infusion) every 4 weeks iv for up to 26 cycles or until progression or other discontinuation criteria are met.
SoC SBRT + Osimertinib Therapy (Osimertinib cohort, single-arm, open-label separate cohort)
EXPERIMENTALSBRT Osimertinib 80mg every day \[qd\] for oral administration up to 36 months or until progression. Osimertinib treatment should start within 7 to 14 days after completion of SBRT
Interventions
Durvalumab 1500 mg every 4 weeks \[q4w\] intravenously \[iv\] for up to 26 cycles or until progression or other discontinuation criteria are met.
Matching placebo for infusion every 4 weeks iv for up to 26 cycles or until progression or other discontinuation criteria are met.
Osimertinib 80 mg every day \[qd\] orally for up to 36 months or until progression or other discontinuation criteria are met. Osimertinib treatment should start from 7 to 14 days after completion of SBRT
Eligibility Criteria
You may qualify if:
- Age ≥18 years
- Planned SoC SBRT as definitive treatment
- World Health Organization (WHO)/ECOG PS of 0, 1 or 2
- Life expectancy of at least 12 weeks
- Body weight \>30 kg
- Submission of tumor tissue sample if available
- Adequate organ and marrow function required
- Patients with central or peripheral lesions are eligible
- Staging studies must be done during screening (PET-CT within 10 weeks)
- Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
You may not qualify if:
- Mixed small cell and non-small cell cancer
- History of allogeneic organ transplantation
- History of another primary malignancy with exceptions
- History of active primary immunodeficiency
- Epidermal growth factor receptor local testing is strongly recommended prior to enrollment. Patients with a tumor harboring an EGFRm per local testing will be excluded from the main cohort
- Prior exposure to immune-mediated therapy with exceptions
- Age ≥18 years
- Planned SoC SBRT as definitive treatment
- WHO/ECOG PS of 0, 1, or 2
- Patients with central or peripheral lesions are eligible
- Patients with a history of metachronous NSCLC and synchronous lesions are eligible with some exceptions
- Staging studies must be done during screening (PET-CT within 10 weeks)
- Submission of tumor tissue sample if available
- Confirmation by local laboratory that the tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R)
- Adequate bone marrow reserve or organ function required
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (209)
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Tuscaloosa, Alabama, 35401, United States
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Chandler, Arizona, 85224, United States
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Phoenix, Arizona, 85004, United States
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Tucson, Arizona, 85719, United States
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Duarte, California, 91010, United States
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Long Beach, California, 90806, United States
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Los Angeles, California, 90095, United States
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San Diego, California, 92123, United States
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Newark, Delaware, 10709, United States
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Washington D.C., District of Columbia, 20010, United States
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Bay Pines, Florida, 33744, United States
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Jacksonville, Florida, 32256, United States
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Miami Beach, Florida, 33140, United States
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Orlando, Florida, 32804, United States
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Atlanta, Georgia, 30322, United States
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Atlanta, Georgia, 30342, United States
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Chicago, Illinois, 60611, United States
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Chicago, Illinois, 60612, United States
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Chicago, Illinois, 60637, United States
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Decatur, Illinois, 62526, United States
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Elmhurst, Illinois, 60126, United States
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Naperville, Illinois, 60540, United States
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Fort Wayne, Indiana, 46845, United States
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Cedar Rapids, Iowa, 52403, United States
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Iowa City, Iowa, 52242, United States
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Elizabethtown, Kentucky, 42701, United States
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Lexington, Kentucky, 40503, United States
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Louisville, Kentucky, 40202, United States
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Metairie, Louisiana, 70006, United States
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New Orleans, Louisiana, 70121, United States
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South Portland, Maine, 04106, United States
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Annapolis, Maryland, 21401, United States
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Baltimore, Maryland, 21201, United States
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Rosedale, Maryland, 21237, United States
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Silver Spring, Maryland, 20910, United States
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Towson, Maryland, 21204, United States
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Boston, Massachusetts, 02215, United States
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Ann Arbor, Michigan, 48197, United States
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Detroit, Michigan, 48201, United States
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Royal Oak, Michigan, 48073, United States
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Duluth, Minnesota, 55805, United States
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Rochester, Minnesota, 55905, United States
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St Louis, Missouri, 63110, United States
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Omaha, Nebraska, 68105, United States
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Las Vegas, Nevada, 89135, United States
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Lebanon, New Hampshire, 03756, United States
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Camden, New Jersey, 08103, United States
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Paramus, New Jersey, 07652, United States
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Albany, New York, 12206, United States
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East Syracuse, New York, 13057, United States
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New Hyde Park, New York, 11042, United States
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New York, New York, 10016, United States
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Rochester, New York, 14642, United States
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Stony Brook, New York, 11794, United States
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Syracuse, New York, 13210, United States
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The Bronx, New York, 10461, United States
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The Bronx, New York, 10467, United States
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Winston-Salem, North Carolina, 27157, United States
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Grand Forks, North Dakota, 58201, United States
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Akron, Ohio, 44304, United States
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Cincinnati, Ohio, 45219, United States
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Cincinnati, Ohio, 45226, United States
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Cleveland, Ohio, 44106, United States
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Portland, Oregon, 97210, United States
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Portland, Oregon, 97213, United States
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Philadelphia, Pennsylvania, 19107, United States
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Pittsburgh, Pennsylvania, 15212, United States
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Charleston, South Carolina, 29425, United States
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Sioux Falls, South Dakota, 57105, United States
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Watertown, South Dakota, 57201, United States
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Austin, Texas, 78745, United States
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Dallas, Texas, 75235, United States
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Houston, Texas, 77030, United States
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Sherman, Texas, 75090, United States
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Burlington, Vermont, 05401, United States
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Richmond, Virginia, 23249, United States
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Bellingham, Washington, 98225, United States
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Seattle, Washington, 98195, United States
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Spokane Valley, Washington, 99216, United States
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Milwaukee, Wisconsin, 53226, United States
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Clayton, 3168, Australia
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Aalst, 9300, Belgium
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Charleroi, 6000, Belgium
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Edegem, 2650, Belgium
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Barretos, 14784-400, Brazil
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Porto Alegre, 90110-270, Brazil
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Recife, 52010-075, Brazil
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Rio de Janeiro, 22271-110, Brazil
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São Paulo, 01327-001, Brazil
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Volta Redonda, 27258-000, Brazil
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Edmonton, Alberta, T6G 1Z2, Canada
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London, Ontario, N6A 5W9, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Montreal, Quebec, H2X 3E4, Canada
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Beijing, 100021, China
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Beijing, 100142, China
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Changchun, 130021, China
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Changsha, 410013, China
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Chengdu, 610042, China
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Fuzhou, 350005, China
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Hangzhou, 310002, China
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Hangzhou, 310022, China
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Hefei, 230031, China
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Jinan, 250117, China
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Nanjing, 210009, China
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Shanghai, 200002, China
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Shanghai, 200030, China
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Shanghai, 200032, China
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Shanghai, 200433, China
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Shenyang, 100003, China
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Suzhou, 215006, China
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Wenzhou, 325000, China
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Wuhan, 430022, China
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Wuhan, 430030, China
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Zhengzhou, 450008, China
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Bron, 69677, France
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Dijon, 21079, France
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Lyon, 69317, France
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Nantes, 44202, France
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Pierre-Bénite, 69310, France
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Toulouse, 31000, France
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Villejuif, 94805, France
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Dresden, 01307, Germany
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Göttingen, 37075, Germany
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Halle, 06120, Germany
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Hanover, 30459, Germany
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Heidelberg, 69126, Germany
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Homburg, 66424, Germany
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Regensburg, 93053, Germany
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Trier, 54292, Germany
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Athens, 11526, Greece
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Athens, 11527, Greece
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Thessaloniki, 55236, Greece
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Haifa, 31096, Israel
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Jerusalem, 91120, Israel
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Kfar Saba, 95847, Israel
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Petah Tikva, 49100, Israel
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Ramat Gan, 52621, Israel
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Tel Aviv, 64239, Israel
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Florence, 50134, Italy
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Genova, 16132, Italy
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Milan, 20132, Italy
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Orbassano, 10043, Italy
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Padova, 35128, Italy
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Pavia, 27100, Italy
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Roma, 00128, Italy
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Rozzano, 20089, Italy
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Akashi-shi, 673-8558, Japan
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Bunkyō City, 113-8677, Japan
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Chūōku, 104-0045, Japan
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Fukuoka, 812-8582, Japan
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Hirosaki-shi, 036-8563, Japan
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Hiroshima, 734-8551, Japan
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Kobe, 650-0047, Japan
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Niigata, 951-8566, Japan
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Osaka, 541-8567, Japan
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Sakaishi, 591-8555, Japan
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Sapporo, 060-8648, Japan
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Sunto-gun, 411-8777, Japan
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Toyoake-shi, 470-1192, Japan
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Yokohama, 241-8515, Japan
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Amsterdam, 1081 HV, Netherlands
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Groningen, 9713 GZ, Netherlands
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Utrecht, 3584 CX, Netherlands
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Bydgoszcz, 85-796, Poland
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Elblag, 02-300, Poland
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Gdansk, 80-952, Poland
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Katowice, 40-514, Poland
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Lodz, 93-513, Poland
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Warsaw, 02-781, Poland
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Hato Rey, 00917, Puerto Rico
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Kazan, Tatarstan, 420029, Russia
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Moscow, 105229, Russia
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Moscow, 115478, Russia
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Moscow, 119421, Russia
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Saint Petersburg, 197758, Russia
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Ufa, 450054, Russia
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Yekaterinburg, 620905, Russia
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Cheongju-si, 28644, South Korea
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Goyang-si, 10408, South Korea
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Gyeonggi-do, 13620, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Badajoz, 6006, Spain
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Barcelona, 08041, Spain
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L'Hospitalet de Llobregat, 08907, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Madrid, 28046, Spain
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Málaga, 29010, Spain
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San Sebastián, 20014, Spain
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Santiago de Compostela, 15706, Spain
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Seville, 41013, Spain
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Valencia, 46010, Spain
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Zaragoza, 50009, Spain
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Ankara, 06010, Turkey (Türkiye)
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Ankara, 06520, Turkey (Türkiye)
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Istanbul, 34214, Turkey (Türkiye)
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Izmir, 35340, Turkey (Türkiye)
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Kocaeli, 41400, Turkey (Türkiye)
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Birmingham, B9 5SS, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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London, EC1A 7BE, United Kingdom
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Manchester, M20 4BX, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Double- Blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 25, 2019
First Posted
February 6, 2019
Study Start
March 6, 2019
Primary Completion (Estimated)
October 31, 2028
Study Completion (Estimated)
October 31, 2028
Last Updated
April 23, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.